title: A chimeric RNA characteristic of rhabdomyosarcoma in normal myogenesis process.
abstract: Gene fusions and their chimeric products are common features of neoplasia. Given that many cancers arise by the dysregulated recapitulation of processes in normal development, we hypothesized that comparable chimeric gene products may exist in normal cells. Here, we show that a chimeric RNA, PAX3-FOXO1, identical to that found in alveolar rhabdomyosarcoma, is transiently present in cells undergoing differentiation from pluripotent cells into skeletal muscle. Unlike cells of rhabdomyosarcoma, these cells do not seem to harbor the t(2;13) chromosomal translocation. Importantly, both PAX3-FOXO1 RNA and protein could be detected in the samples of normal fetal muscle. Overexpression of the chimera led to continuous expression of MYOD and MYOG-two myogenic markers that are overexpressed in rhabdomyosarcoma cells. Our results are consistent with a developmental role of a specific chimeric RNA generated in normal cells without the corresponding chromosomal rearrangement at the DNA level seen in neoplastic cells presumably of the same lineage.
  
  
  CONCLUSIONS
  A chimeric fusion RNA, PAX3-FOXO1, associated with alveolar rhabdomyosarcoma, is also present in normal non-cancer cells and tissues. Its transient expression nature and the absence of t(2;13) chromosomal translocation are consistent with a posttranscriptional mechanism. When constantly expressed, PAX3-FOXO1 interfered with the muscle differentiation process, which presumably contributes to tumorigenesis.
authors.affiliation: 1Department of Pathology and 2University of Virginia Cancer Center, University of Virginia, Charlottesville, Virginia; and 3Department of Pathology, Yale University, New Haven, Connecticut.
authors.forename: Huiling
authors.initials: H
authors.lastname: Yuan
authors.forename: Fujun
authors.initials: F
authors.lastname: Qin
authors.forename: Mercedeh
authors.initials: M
authors.lastname: Movassagh
authors.forename: Hong
authors.initials: H
authors.lastname: Park
authors.forename: Wendy
authors.initials: W
authors.lastname: Golden
authors.forename: Zhongqiu
authors.initials: Z
authors.lastname: Xie
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Sklar
authors.forename: Hui
authors.initials: H
authors.lastname: Li
mesh_terms: D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D050939:Gene Fusion; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D024510:Muscle Development / Q000235:genetics*; D009132:Muscles / Q000196:embryology / Q000378:metabolism*; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D018008:Myogenin / Q000235:genetics / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics* / Q000378:metabolism; D018232:Rhabdomyosarcoma, Alveolar / Q000235:genetics* / Q000378:metabolism; D014178:Translocation, Genetic
chemical_list: C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D017570:MyoD Protein; D018008:Myogenin; D015514:Oncogene Proteins, Fusion; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051761:Paired Box Transcription Factors